Inhibition of bacterial oxidases by formamide and analogs.
The enzymatic activity of Paracoccus denitrificans cytochrome c oxidase (COX) and Escherichia coli cytochrome b(o) ubiquinol oxidase (QOX) was determined in the presence of formamide, N,N-dimethyl formamide and N,N-dimethyl acetamide. Formamide was found to inhibit the enzyme activity of the oxidases most significantly, whereas the other two compounds inhibited the activity to a lesser extent. The effects of formamide and analogs on enzyme activity were very similar for COX and QOX, indicating that the mechanism of inhibition might be the same for both of these oxidases. The inhibition kinetics followed a non-competitive mechanism. Studies using proteoliposomes of COX and QOX containing the electron entry site of the enzyme directed towards the outside of the vesicles showed that the effect of inhibition by formamide was higher when the inhibitor was present on the outside of the proteoliposome compared to when it was present only in the aqueous core. This indicates that inhibition of enzyme activity by formamide possibly predominantly involves blocking of the water exit pathway in the oxidases.
Gupta
Sayan
S
Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India.
Mazumdar
Shyamalava
S
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology*; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D005559:Formamides / Q000494:pharmacology*; D008081:Liposomes / Q000276:immunology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010231:Paracoccus denitrificans / Q000187:drug effects / Q000201:enzymology; D010743:Phospholipids / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D005559:Formamides; D008081:Liposomes; D010743:Phospholipids; D010088:Oxidoreductases; C038862:cytochrome o oxidase; D003576:Electron Transport Complex IV